Osseous lesions in the oral cavity and elsewhere in the body are the result of disequilibrium between bone formation and bone resorption. However, it is not always clear which of the two factors predominates. For example, the loss of bone associated with severe periodontitis may be the result of enhanced osteoclastic activity, non-osteoclastic bone resorption or a reduced rate of bone formation. In any case, periodontal disease is a major contributing factor to tooth loss in the United States and affects millions of individuals. The amount of bone lost or gained is generally a function of the number and relative activity of osteoblasts and osteoclasts. The number of these cells is governed by a variety of factors including the size of the osteoprogenitor pools and the rates of precursor proliferation, differentiation, and, ultimately, cell death. There is now strong but still largely circumstantial evidence that the circultaing monocyte is the precursor of the osteoclast. We propose to: (1) directly assess the osteoclast-forming potential of monocytes and mononuclear phagocytes; (2) determine whether agents which promote osteoclast proliferation, such as parathyroid hormone, work, in vivo, by stimulating monocyte production and migration; (3) establish whether monocytopenia, monocytosis or RES blockade affects the steady-state size of the osteoclast pool or alters the response of osteoclast precursors to stimulation; (4) assess the role of bone matrix and matrix-degradation products in osteoclast differentiation in vitro.